Hepatitis B vaccines have been available for many years (e.g. see chapter 16 of reference 1), and their active ingredient is the surface antigen (HBsAg) from hepatitis B virus (HBV). The original HBV vaccines used HBsAg that had been purified from human blood, but vaccines based on recombinantly-expressed HBsAg became widely available in the 1990s. Since then, HBsAg has also been incorporated as a component in multivalent vaccines i.e. vaccines containing a mixture of immunogens from more than one pathogen, such that administration of the vaccine can simultaneously immunize a subject against more than one pathogen. These multivalent vaccines typically include HBsAg plus at least ‘DTP’ (diphtheria, tetanus and pertussis) antigens.
The original monovalent recombinant HBV vaccine, ENGERIX B™, includes an aluminum hydroxide adjuvant. More recently, monovalent HBV vaccines based on more modern adjuvants have become available e.g. using the ‘AS04’ adjuvant [2] in the FENDRIX™ product from GSK, the RC-529 adjuvant in the SUPERVAX™ product from Berna Biotech, or CpG oligonucleotide adjuvants such as CPG7909 [3] from Coley Pharmaceuticals.
For recombinant expression of HBsAg a variety of systems have been described. Expression hosts that have been used include bacteria, yeasts (including Saccharomyces, Hanensula and Pichia species), mammalian cell culture (including CHO cells, COS cells, Bu3 cells), insect cells (using baculovirus vectors), and plant cells (e.g. for ‘edible vaccines’).
It is an object of the invention to provide further and improved systems for recombinant expression of HBsAg, particularly for preparing HBsAg to be used in combination vaccines (such as those containing DTP antigens) or in new monovalent HBV vaccines.